N-(substituted indazolyl-n1-methyl)alkyleneimines and their use as biocides

ABSTRACT

COMPOUNDS THAT HAVE THE STRUCTURAL FORMULA   1-(R=N-CH2-),3-Y,(X)N-INDAZOLE   WHEREIN X REPRESENTS HALOGEN, NITRO, AMINO, ACETAMINO, AROYLAMINO, OR (HALOBENZYLIDENE) AMINO; Y REPRESENTS HYDROGEN OR HALOGEN; R REPRESENTS AN ALKYLENE GROUP HAVING FROM 4 TO 8 CARBON ATOMS; AND N REPRESENTS AN INTEGER IN THE RANGE OF ZERO TO 2 CAN BE USED TO CONTROL THE GROWTH OF MICROORGANISMS. ILLUSTRATIVE OF THESE COMPOUNDS ARE N-(5-NITROINDAZOLYL-N1-METHYL)HEXAMETHYLENEIMINE AND N-(3-CHLOROINDAZOLYL-N1-METHYL)PIPERIDINE.

Presser Patented Oct. 16, 1973 3,766,192 N-(SUBSTITUTED INDAZOLYL-N METHYL) ALKYLENEIMINES AND THEIR USE AS BIOCIDES Pasquale Paul Minieri, Woodside, N.Y., assiguor to Tenneco Chemicals, Inc.

No Drawing. Continuation-impart of applications Ser. No. 689,812, Dec. 12, 1967, now Patent No. 3,641,050, dated Feb. 8, 1972, and Ser. No. 141,999, May 10, 1971. This application Nov. 22, 1971, Ser. No. 201,159

Int. Cl. C0711 49/18 U.S. Cl. 260293.6 11 Claims ABSTRACT OF THE DISCLOSURE Compounds that have the structural formula C--Y Xu (JHn-N=R wherein X represents halogen, nitro, amino, acetamino, aroylamino, or (halobenzylidene)amino; Y represents hydrogen or halogen; R represents an alkylene group having from 4 to 8 carbon atoms; and n represents an integer in the range of zero to 2 can be used to control the growth of microorganisms. Illustrative "of these compounds are N-(S-nitroindazolyl-N -methy1)hefiamethyleneimine and N- 3-chloroind azolyl-N -methyl piperidine.

c H,-N=R wherein X represents chlorine, bromine, fluorine, iodine, nitro, amino, acetamino, aroylamino, or (halobe nzylidene)amino; Y represents hydrogen, chlorine, bromine, fluorine, or iodine; R represents an alkylene group having from 4 to 8 carbon atoms; and n represents an integer in the range of zero to 2.

Particularly effective as biocides are the compounds represented by the structural formula wherein X represents nitro, chlorine, or (chlorobenzylidene)amino; Y represents hydrogen or chlorine; R represents a branched or unbranched alkylene group having 5 or 6 carbon atoms; and n represents an integer in the range of zero to 2. Illustrative of these preferred compounds are the following N-(3-chloroindazolyl-N -methyl)piperidine,

N- 3-chloro-5 -nitroindazolyl-N -methyl) piperidine,

N- 5,6-dinitroindazolyl-N -methyl piperidine,

N- (6-nitroindazolyl-N -methyl) piperidine,

N-(5-chloroindazolyl-N -methyl)-3-methylpiperidine,

N- (3 -chloroindazolyl-N -methyl hex amethyleneimine,

N-(S-chloroindazolyl-N -methyl)hexamethyleneimine,

N-(6-chloroindazolyl-N -methyl)hexamethyleneimine,

N-(3,S-dichloroindazolyl-N -methyl)hexamethyleneimine,

N-(3,6-dichloroindazolyl-N -methyl)hexamethylene- 1m1ne,

N-(3,5,6-trichloroindazolyl-N -methyl)hexamethyleneimine,

N-(3-chloro-5-nitroindazolyl-N -methyl)hexamethyleneimine,

N- (3 -chloro-6-nitroindazolyl-N -methyl) hexamethyleneimine,

N-(3,S-dichloroindazolyl-N -methyl)hexamethyleneimine,

N- 5 ,6-dinitroindazolyl-N -methyl) hexamethyleneimine,

and the like.

The novel compounds may be prepared by any suitable and convenient procedure. For example, they may be prepared by heating the appropriate N -hydroxymethylsubstituted-indazole with an alkyleneimine. The reaction is preferably carried out in a solvent, such as benzene, toluene, pyridine, or acetone, at the reflux temperature of the reaction mixture. The N -hydroxymethyl-substituted-indazoles may be prepared by the procedure described in my copending application Ser. No. 589,235, now U.S. Pat. 3,637,736, issued Jan. 12, 1972, which was filed on Oct. 25, 1966, v

The compounds of this invention can be used to con-= trol the growth of a wide variety of bacteria, fungi, and other microorganisms. They are of particular value as biocides in surface-coating compositions including both organic-solvent-based and water-based coating systems.

In a preferred embodiment of the invention, the novel compounds are used as biocides in aqueous compositions that contain about 10 percent to 60 percent by weight of a water-insoluble resinous binder that is a synthetic linear addition polymer and/or an oleoresinous binder. The useful aqueous dispersions of synthetic linear addition polymers are ordinarily prepared by the emulsion polymerization of monoethylenically-unsaturated monomers. Illustrative of these polymers are polyvinyl acetate;

polyvinyl butyrate; polyvinyl chloride; copolymers of vinyl acetate with vinyl chloride or acrylonitrile; copolymers of vinyl chloride with acrylonitrile or vinylidene chloride; polyethylene; polyisobutylene; copolymers of styrene with butadiene, acrylonitrile, or maleic anhydrid'e; copolymers of acrylic acid esters or methacrylic acid esters of alcohols having 1 to 8 carbon atoms with vinyl acetate, vinyl chloride, acrylonitrile, or styrene; copolymers of the aforementioned acrylic acid esters, the

aforementioned methacrylic acid esters, and acrylic acid;

and mixtures thereof. Suitable oleoresinous binders in,-

elude drying oils, bodied drying oils, oleo-resinous var= nishes, alkyd resins, and mixtures thereof.

In another preferred embodiment of the invention, the novel compounds are used as the biocides in organicsolvent-based systems that contain an oleoresinous binder 4 EXAMPLE 2 A mixture: of 1 25 ml. of dry toluene, 18.3- grams (0.1

mole) of N hydroxymethyl-S-chloroindazole, and 10 grams (0.1 mole) of hexamethylcneimine was heated at as hereinbefore defined 5 its. reflux temperature until the theoretical quantity (1.8 o a small concentration of the biocidal compound ml.) of Water hacl been evolved and then for an additional is required to protect the surface-coating composition 30 mmutesati this temperature The macho mixture from attack by microorganisms. As little as 0.10 percent heated water b under reduced Pressure H of one or more of these compounds, based on the weight reacheit constant i :rhere was obtamed 100 of the composition, will bring about an appreciable imcent i i oi f ?9 provement in the resistance of the composition to attack ylenelmme hqmd whlch sohdlfied on Standmg' The by microorganisms. Five percent or more of the biocidal Product m percgnt Percent compounds can be used, but these larger amounts gen- Percent a 135 Percent (calculatad, P erally do not provide further improvement in the propercent 15.2. percent N, and 12.8 percent Cl). ties of the szirfage-coating goriglolsitiglns and forf tlilis EXAM L 3 reaso are no or man y use 1e e amount 0 t e biocidal compounds that will provide optimum protection A m of 125 of dry 311161162183 grams for a surface-coating composition depends upon such mole) of N1ihydroXymethy1'3s'dlchior9mdazole and 10 factors as the choice of biocidal compound, the choice .grams male) of hexaimthy'lenelmme was heated at of resinous binder and other ingredients of the composi- 20' reflux tempfiramre 1 of waier had beep i and the amount of each that is used and the evolved: and then for an additional minutes at this application for which the coating composition is intended, tempgilmre The mactwn mlxiure was treated wlth i most cases about 025 Percent to 2 Percent of the colorizing carbon and filter aid and then heated on a bi id compound, based on the weight of the surface water bath under reduced pressure until it reached concoating composition is used 25 stant weight. There was obtained a 97.3 percent yield In addition to the resinous binder and the biocidal Pf,N(35fdmh1rmdaZlyN1Jmethynhexamethyleng' compound, the surface-coating compositions may contain lmme, whlch melted at 34 various auxiliary materials, such as pigments, extenders, EXAMPLES 4 9 solvents, dyes, defoammg agents, driers, emulsifiers, 30 t plasticizers, and the like in the amounts ordinarly used A gene? i N'(substltuted lndalolyl'Nl-methyl)hexafor these ur o e methyleneimines was prepared by the procedures de- The biocidal compounds may be incorporated into the scribed in Examples 2 and The compounds P p surface-coating compositions by an convenient procedure. and their properties are given in Table I.

TABLE I Melting Example Method of Yield Foint number Compound preparation (percent) C.)

4 N-[fi-(3,4-dich10mbenzylidene)aminoindazolyl-N Example 2 100.0 Oil methyl]hexamethyleneimine. 5 N-(S-ghlpro5-nitrolndazolyl-N -methyDheXamethyld0 98.7 (B) e N iis ii itgii-e-nitromdazoi i-n -meth 1)hexamethyl- Exam ies 95.3 74-81 N iii n i t r dindazolyl-N -methyl)hexemethylenelmine 93 5 72-82 N-(fi-nitroindazolyl-N -methyl)hexamethyleneimine 91 7 73-83 N-(5,6-dinitroindaz0lyl-N -methy1)hexamethyleneimin 96 6 87-96 B semisolid.

To 200 ml. of toluene, which had been dried by azeotropic distillation, was added with'stirring 18.3 grams (0.1 mole) of N -hydroxymethyl-3-chloroindazole and 10 grams (0.1 mole) of hexamethyleneimine. The re action mixture was heated at its reflux temperature until 1.8 ml. of water had been evolved and then for an ad ditional 30 minutes at this temperature. The reaction mixture was then heated on a water bath under reduced pressure until it reached constant weight. There was obtained 27.7 grams of N-(3-chloroindazolyl-N -methyl) hexamethyleneimine, which contained 63.35 percent C,

6.51 percent H, and 15,62 percent N (calculated, 65.2.

percent C, 6.52 percent H, and 15.2 percent N).

EXAMPLE 10 A mixture of 200 ml. of benzene, 18.3 grams (0.1 mole) of N -hydroxymethyl-5,6-dinitroindazole, and 9.2 grams (0.11; mole) of piperidine was heatedat its reflux temperature until the theoretical quantity (1.8 ml.) of water had been evolved and then for an additional 75 minutes at this temperature. The reaction mixture was heated on a water bath under reduced pressure until it reached constant weight. There was obtained 29' grams (95.3 percent yield) of N-(5,6-dinitroindazolyl-N -methyl)piperidine, which melted at. -133" C. and contained 50.48 percent C, 4.90 percent H, and 22.7 percent N (calculated, 51.1 percent C, 4.92 percent H, and 22.95 percent N). The structure of the compound was confirmed by infra-red analysis.

EXAMPLE 11 ligroin. There was obtained 24 grams (93.8 percent yield) of N-(6-nitroindazolyl-N methyl)piperidine, which melted at 9496 C. and contained 59.98 percent C, 6.19 percent H, and 22.05 percent N (calculated, 59.9

(C) An exterior house paint was prepared by mixing together the following materials:

Parts by weight percent C, 6.15 percent H, and 22.15 percent N). The 5 Basic lead carbonate 288 structure of the compound was confirmed by infra-red Zinc oxide 232 analysis. Titanium dioxide (rutile) 149 EXAMPLES 12-18 Talc d 260 A series of N-(substituted indazolyl-N -methyl) LmsFed P 242 piperidines was prepared by the procedures described in Bqdled 9 9 011 114 Examples 10 and 11. In each case the structure of the l f P 114 compound was confirmed by infra-red analysis. The com- A tlsk g agent 2 pounds prepared and their properties are given in Table Manganese naphthenate (6%) 2.27 IL Lead naphthenate (24%) 11.3

TABLE It Analysis M 1t Example Method of Yield po i r iiz Found percent Calculated percent number Compound preparation (percent) C.) O H N C1 0 H N 01 12 N-(3ehloroindazolyl-N -methyl) Example 0. 100.0

piperidine. 13 3engi o-s-riitroindazolyl-N -methy1) Example11---- 96.7 106-114 54.99 5.25 20.09 52, 5, 95

H18. 14 N ig iiiftgqi dazo1y1-N -met y 91.0 89-91 60.6 6.18 22,4 600 2L6 I118. 15 Ngb ir lgroindazolyl-N m hyD H-11 97.8 104405 1 ,1 1&8 M2

I1 16 N igf iiihioro d y1-N y 96.0 75-78 53. 93 4.58 14.7 25,7 14,8 25.0

n 1118. 17 Ngifi ghloroindazolyl-N et yD- 9 59-65 62.9 6.50 15. 53 14.39 63.7 6,83 15,9 13,

methylpiperidine. 18 N-(5,6-dinitroindazo1yl-N -methy1)-3- Ex ple 10.-....-.- 99.0 108-115 53. 27 5,27 2 3 5L1 2L3 methylpiperidine.

EXAMPLE 19 "To samples of this paint was added 2 percent by (A) A polyvinyl acetate emulsion paint was prepared Welght of the Compounds f this invention by mixing together the following materials: or a comparatlve bloclde- Parts y weight EXAMPLE 20 Water 280 Potassium Pyrophosphate 3 Samples f he paints whose prep ti was described Calcium metasilicate 13 111 mp 9 Were evaluated by the follgwing Proce. Titanium dioxide (rutile) 22 dufel PIFCeS 0f wn paper were dipped into the 2% aqueous solution of methylcellulose 200 paint, dr1ed for 24 hours, and again dipped into the paint. Diethyl ether of diethylene glycol 37 f r a 24-hour drying period, the coated paper samples 55% aqueous dispersion of polyvinyl acetate 350 were cut into 11% inch squares. Each of the coated paper T o samples of this paint was added 2 percent by weight a ii l g g on 1 plate i t and mycophfl'agiar of either one of the compounds of this invention or a f th een ,mocu ated Wlth 1 of 9 1 6951 comparativebiocide 0 b gan1sm. 'I Ihe plates, prepared in triplicate, (B) acrylic paint was prepared by mixing together were mcu ated at 28 C. and observed weekly. v The the following materials: growth was estimated aficordll'lg t0 the following k y, Parts by Weight and the results of the triplicate plates were averaged. In Titanium dioxide 1136 the es that follow Mica (325 mesh waterground) 136 Calcium carbonate 568 Water 699 =Zqne of inhibition in mm 2% aqueous solution of sodiumv salt of male1c O=No Zone of inhibition ggihydride/dnsobutylene copolymer (Tamol 41 Tr=T2ace Zone of inhibition =Not tested Alkyl aryl polyether surfactant (Triton CF-lO) 9 Antofoam agent (Colloid 581B) 18 g A Bacl"s subtllls Ethylene glycol i 9 1 acter'la er aerogenes Hydroxyethyl cellulose (Cellosize QP 4400 9.1 Bacteria? aerugingsq Ammonium hydroxide (28% aqueous solution) 9 Bactenaf DM1Xed moculllm conslstlflg of r glfflwa Aqueous dispersion containing 43% by weight of 10145, aer 0881188 ATCC 7256, and lhfes'llllthe ammonium salt of a copolymer of 66% by ldentlfied strains of Bacillus weight of ethyl acrylate, 32.5% by weight of Fungi E-P-ullularia pullulans methyl methacrylate, and 1.5% by Weight of Fungi F-Penicillium crustosum acrylic acid containing 3% by weight of tert. 70 Fungi GAspergillus niger octylphenoxypolyethoxyethanol 2486 To samples of this paint was added 2 percent by weight of either one of the compounds of this invention The compounds tested and the results obtained are or a comparative biocide. given in Table III.

TABLE III Biocidal activity Effect on Paint Bacteria Fungi, Biocide Paint pH Color A B C D E F G Product of Example:

ZO-5 ZO2 Tr ZO-fi 20-2 1 ZO-l Z'0-2 ZO-2 ZO-3 ZO-l il 20-4 20-5 ZO-Z PVA 8. 2 20-2 ZO-1 ZO-5 6 Acrylic.. 9.7 -..do Z-3 Tr ZO-4 Tr Tr Tr Oil .do ZO-l ZO-l Tr ZO -l Tr ZO- 7 ZO--1 Tr ZO-3 Tr Tr Tr Oil ZO-5 -3 Tr ZO-3 ZO-l ZO-3 8 Acryll Tr ZO-5 Tr Tr Tr Oil". Z0- ZO-2 Tr PVA ZO-l ZO-2 ZO7 9 {Acrylic ZO-l 20-3 Tr Tr Tr Oil Tr Tr Tr PVA- ZO-3 ZO-l ZO-4. Tr 20-2 Tr 12 Acryll ZO-4 ZO-4 ZO-l ZO-l ZO-fi ZO-l [0 d Tr Tr Tr Bis(phenylmercury)- Off-white. s ZO-lO ZO-2 ZO7 ZO-17 Z0-6 ZO-13 dodecenylsuceinate do ZO-9 ZO-d ZO-Q ZO-l ZO-lO (Super Ari-It). do ZO-8 ZO-lO ZO-lO 2,3,5gif-Tetraehloro-4- Ofi-white. Z0-8 0 0 ZO13 20-10 Z0 -9 (mbthyl-sulfonyndo ZO-8 0 0 ZO-13 ZO-7 ZO-G pyridine (Dow 1013). Beige Z0-12 ZO-IO ZO-G Each of the other N-(substituted indazolyl-N -methyl)- alkyleneimines herein disclosed can be used in a similar manner to inhibit or prevent the growth of microorganisms in surface-coating compositions.

The terms and expressions which have been employed are used as terms of description and not of limitation. There is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed.

What is claimed is:

1. A compound having the structural formula -CY X. LL

(|1H7-N=R wherein X represents halogen, nitro, amino, acetamino, aroylamino, or (halobenzylidene)amino; Y represents hydrogen or halogen; R represents an alkylene group having from 4 to 8 carbon atoms; n represents an integer in the range of Zero to 2; and when n represents zero, Y represents halogen.

2. A compound as set forth in claim 1 that has the structural formula .C YI X 1 II N wherein X represents nitro, chlorine, or (chlorobenzyli= dene)amino; Y represents hydrogen or chlorine; R mp resents an alkylene group having from 5 to 6 carbon atoms; n represents an integer in the range of zero to 2; and when n represents zero, Y' represents chlorine.

3. A compound as set forth in claim 2 wherein N=R' represents a piperidine group.

4. A compound as set forth in claim 2 wherein N=R' represents a hexamethyleneimine group.

5. A compound as set forth in claim 2 wherein X is chlorine and n is l.

6. A compound as set forth in claim 2 wherein X is nitro and n is 1.

7. The compound as set forth in claim 2 that is N-(3- chloroindazolyl-N -methyl)piperidine.

8. The compound as set forth in claim 2 that is N-(3- chloro-6-nitroindazolyl-N -methyl)hexamethyleneimine.

9. The compound as set forth in claim 2 that is N-(3,5-*'

dichloroindazolyl-N -methyl)hexamethyleneimine.

10. The compound as set forth in claim 2 that is N- (5,6-dinitroindazolyl-N -methyl)hexamethyleneimine.

11. The compound as set forth in claim 2 that is N-(S- chloroindazolyl-N -methyl)-3-methylpiperidine.

JOHN D. RANDOLPH, Primary Examiner US. Cl. X.R.

106-15, 17; 424267, 273; 26045.8 N, 240 G, 310 C 

